tbuckley/cabot-search huggingface dataset:
Digital solutions for early breast cancer detection
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2023)

By 2040, more than 3 million new cases of breast cancer and 1 million deaths are estimated to occur each year worldwide. Identifying those at greatest risk of developing life-threatening breast cancers is a public-health priority. In this issue of The Lancet Digital Health, Ash Kieran Clift and colleagues developed and evaluated four prognostic models to predict 10-year risk of breast cancer mortality in women aged 20–90 years. The best performing model could be used to identify women at high risk of mortality, including those too young for breast cancer screening.
Ultraviolet Light‐Based Micropattern Printing on Titanium Surfaces to Promote Early Osseointegration (Adv. Healthcare Mater. 21/2023)
Authors: Yiting Lou, Mouyuan Sun, Jingyu Zhang, Yu Wang, Haiying Ma, Zheyuan Sun, Shengjie Li, Xiaoyan Weng, Binbin Ying, Chao Liu, Mengfei Yu, Huiming Wang
Journal: Advanced Healthcare Materials (2023)

Platelet Membranes In article 2203300 by Binbin Ying, Chao Liu, Mengfei Yu, and co-workers, ultraviolet light-based micropattern printing is designed to obtain high-resolution linear micropattern. This simple strategy offers a microfabrication method that can be extended to manufacture various shape- and size-controlled micropatterns on titanium implants as well as provide insight into the surface structure design for enhanced bone regeneration.
Cellular senescence primes liver fibrosis regression through Notch‐EZH2
Authors: Ping Song, Juan‐Li Duan, Jian Ding, Jing‐Jing Liu, Zhi‐Qiang Fang, Hao Xu, Zhi‐Wen Li, Wei Du, Ming Xu, Yu‐Wei Ling, Fei He, Kai‐Shan Tao, Lin Wang
Journal: MedComm (2023)

Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single-cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti-inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the change of the epigenetic regulator enhancer of zeste homolog2 (EZH2) accompanied with the emergence of hepatic senescent cells while liver fibrosis regressed. Blocking EZH2 signaling by EPZ6438 reduced hepatic senescent cells and macrophages, decelerating liver fibrosis regression. Moreover, the promoter region of EZH2 was transcriptionally suppressed by Notch-Hes1 (hairy and enhancer of split 1) signaling. Disruption of Notch in macrophages using Lyz2 (lysozyme 2)
Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial
Authors: Xiaoqin Li, Shan Hu, Jiawei Yin, Xiaobo Peng, Lei King, Linyan Li, Zihui Xu, Li Zhou, Zhao Peng, Xiaolei Ze, Xuguang Zhang, Qiangchuan Hou, Zhilei Shan, Liegang Liu
Journal: Gut Microbes (2023)

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a <i>KRAS</i> G12C Mutation
Authors: Adrian Sacher, Patricia LoRusso, Manish R. Patel, Wilson H. Miller, Elena Garralda, Martin D. Forster, Armando Santoro, Alejandro Falcon, Tae Won Kim, Luis Paz-Ares, Samantha Bowyer, Maria de Miguel, Sae-Won Han, Matthew G. Krebs, Jong-Seok Lee, Michael L. Cheng, Kathryn Arbour, Erminia Massarelli, Yoonha Choi, Zhen Shi, Sandhya Mandlekar, Mark T. Lin, Stephanie Royer-Joo, Julie Chang, Neekesh V. Dharia, Jennifer L. Schutzman, Jayesh Desai
Journal: New England Journal of Medicine (2023)

Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation. The primary objective was an assessment of safety; pharmacokinetics, investigator-evaluated antitumor activity, and biomarkers of response and resistance were also assessed.A total of 137 patients (60 with non-small-cell lung cancer [NSCLC], 55 with colorectal cancer, and 22 with other solid tumors) received divarasib. No dose-limiting toxic effects or treatment-related deaths were reported. Treatment-related adverse events occurred in 127 patients (93%); grade 3 events occurred in 15 patients (11%) and a grade 4 event in 1 patient (1%). Treatment-related adverse events resulted in a dose reduction in 19 patients (14%) and discontinuation of treatment in 4 patients (3%). Among patients with NSCLC, a confirmed response was observed in 53.4% of patients (95% confidence interval [CI], 39.9 to 66.7), and the median progression-free survival was 13.1 months (95% CI, 8.8 to could not be estimated). Among patients with colorectal cancer, a confirmed response was observed in 29.1% of patients (95% CI, 17.6 to 42.9), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.2). Responses were also observed in patients with other solid tumors. Serial assessment of circulating tumor DNA showed declines in KRAS G12C variant allele frequency associated with response and identified genomic alterations that may confer resistance to divarasib.Treatment with divarasib resulted in durable clinical responses across KRAS G12C-positive tumors, with mostly low-grade adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT04449874.).
Anti–Insulin Receptor Antibody for Malignant Insulinoma and Refractory Hypoglycemia
Authors: Soravis Osataphan, Maria Vamvini, Evan D Rosen, Lei Pei, Natanie Erlikh, Gurcharan Singh, Poojaben Dhorajiya, J Anthony Parker, Jonathan M Dreyfuss, Ahmed Rattani, Mary-Elizabeth Patti
Journal: New England Journal of Medicine (2023)
A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis
Authors: Soo‐Yeon Kang, Masaki Kimura, Sunil Shrestha, Phillip Lewis, Sangjoon Lee, Yuqi Cai, Pranav Joshi, Prabha Acharya, Jiafeng Liu, Yong Yang, J. Guillermo Sanchez, Sriramya Ayyagari, Eben Alsberg, James M. Wells, Takanori Takebe, Moo‐Yeal Lee
Journal: Advanced Healthcare Materials (2023)

Abstract Human organoids have the potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo. This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high‐throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale‐up and quality control. Using organoids for HTS is further challenged by the lack of easy‐to‐use fluidic systems that are compatible with relatively large organoids. Here, these challenges are overcome by engineering “microarray three‐dimensional (3D) bioprinting” technology and associated pillar and perfusion plates for human organoid culture and analysis. High‐precision, high‐throughput stem cell printing, and encapsulation techniques are demonstrated on a pillar plate, which is coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels are differentiated into liver and intestine organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384‐well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.
Seroprevalence, seroconversion and seroreversion of Borrelia burgdorferi-specific IgG antibodies in two population-based studies in children and adolescents, Germany, 2003 to 2006 and 2014 to 2017
Authors: Stefanie Böhm, Tom Woudenberg, Klaus Stark, Merle M Böhmer, Katharina Katz, Ronny Kuhnert, Martin Schlaud, Hendrik Wilking, Volker Fingerle
Journal: Eurosurveillance (2023)

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi (Bb), is the most common tick-borne infection in Germany. Antibodies against Bb are prevalent in the general population but information on temporal changes of prevalence and estimates of seroconversion (seroincidence) and seroreversion are lacking, especially for children and adolescents.AimWe aimed at assessing antibodies against Bb and factors associated with seropositivity in children and adolescents in Germany.MethodsWe estimated seroprevalence via two consecutive cross-sectional surveys (2003-2006 and 2014-2017). Based on a longitudinal survey component, we estimated annual seroconversion/seroreversion rates.ResultsSeroprevalence was 4.4% (95% confidence interval (CI): 3.9-4.9%) from 2003 to 2006 and 4.1% (95% CI: 3.2-5.1%) from 2014 to 2017. Seroprevalence increased with age, was higher in male children, the south-eastern regions of Germany and among those with a high socioeconomic status. The annual seroconversion rate was 0.3% and the annual seroreversion rate 3.9%. Males were more likely to seroconvert compared with females. Low antibody levels were the main predictor of seroreversion.ConclusionWe did not detect a change in seroprevalence in children and adolescents in Germany over a period of 11 years. Potential long-term changes, for example due to climatic changes, need to be assessed in consecutive serosurveys. Seroconversion was more likely among children and adolescents than among adults, representing a target group for preventive measures. Seroreversion rates are over twice as high in children and adolescents compared with previous studies among adults. Thus, seroprevalence estimates and seroconversion rates in children are likely underestimated.
Cases of Crimean-Congo haemorrhagic fever in North Macedonia, July to August 2023
Authors: Dejan Jakimovski, Krsto Grozdanovski, Goran Rangelov, Verica Pavleva, Pavle Banović, Alejandro Cabezas-Cruz, Katerina Spasovska
Journal: Eurosurveillance (2023)

The last report of Crimean-Congo haemorrhagic fever (CCHF) in North Macedonia was more than 50 years ago in the northwest. We report on a fatal CCHF case following a Hyalomma tick bite in the east of the country in July 2023. Tracing of 67 contacts identified CCHF in one healthcare worker (HCW) providing care for the patient. Monitoring of contacts is concluded (including further 11 HCW contacts), thus far 28 days after the death of the case no additional cases were identified.
Trained immunity of alveolar macrophages enhances injury resolution via KLF4-MERTK-mediated efferocytosis
Authors: Sreeparna Chakraborty, Abhalaxmi Singh, Li Wang, Xinge Wang, Mark A. Sanborn, Zijing Ye, Mark Maienschein-Cline, Amitabha Mukhopadhyay, Balaji B. Ganesh, Asrar B. Malik, Jalees Rehman
Journal: The Journal of Experimental Medicine (2023)

Recent studies suggest that training of innate immune cells such as tissue-resident macrophages by repeated noxious stimuli can heighten host defense responses. However, it remains unclear whether trained immunity of tissue-resident macrophages also enhances injury resolution to counterbalance the heightened inflammatory responses. Here, we studied lung-resident alveolar macrophages (AMs) prechallenged with either the bacterial endotoxin or with Pseudomonas aeruginosa and observed that these trained AMs showed greater resilience to pathogen-induced cell death. Transcriptomic analysis and functional assays showed greater capacity of trained AMs for efferocytosis of cellular debris and injury resolution. Single-cell high-dimensional mass cytometry analysis and lineage tracing demonstrated that training induces an expansion of a MERTKhiMarcohiCD163+F4/80low lung-resident AM subset with a proresolving phenotype. Reprogrammed AMs upregulated expression of the efferocytosis receptor MERTK mediated by the transcription factor KLF4. Adoptive transfer of these trained AMs restricted inflammatory lung injury in recipient mice exposed to lethal P. aeruginosa. Thus, our study has identified a subset of tissue-resident trained macrophages that prevent hyperinflammation and restore tissue homeostasis following repeated pathogen challenges.
Targeting the gut microbiota with dietary fibers: a novel approach to prevent the development cardiovascular complications linked to systemic lupus erythematosus in a preclinical study
Authors: Javier Moleón, Cristina González-Correa, Iñaki Robles-Vera, Sofía Miñano, Néstor de la Visitación, Antonio Manuel Barranco, Natividad Martín-Morales, Francisco O’Valle, Laura Mayo-Martínez, Antonia García, Marta Toral, Rosario Jiménez, Miguel Romero, Juan Duarte
Journal: Gut Microbes (2023)

This study is to investigate whether dietary fiber intake prevents vascular and renal damage in a genetic mouse model of systemic lupus erythematosus (SLE), and the contribution of gut microbiota in the protective effects. Female NZBWF1 (SLE) mice were treated with resistant-starch (RS) or inulin-type fructans (ITF). In addition, inoculation of fecal microbiota from these experimental groups to recipient normotensive female C57Bl/6J germ-free (GF) mice was performed. Both fiber treatments, especially RS, prevented the development of hypertension, renal injury, improved the aortic relaxation induced by acetylcholine, and the vascular oxidative stress. RS and ITF treatments increased the proportion of acetate- and butyrate-producing bacteria, respectively, improved colonic inflammation and integrity, endotoxemia, and decreased helper T (Th)17 proportion in mesenteric lymph nodes (MLNs), blood, and aorta in SLE mice. However, disease activity (splenomegaly and anti-ds-DNA) was unaffected by both fibers. T cell priming and Th17 differentiation in MLNs and increased Th17 infiltration was linked to aortic endothelial dysfunction and hypertension after inoculation of fecal microbiota from SLE mice to GF mice, without changes in proteinuria and autoimmunity. All these effects were lower in GF mice after fecal inoculation from fiber-treated SLE mice. In conclusion, these findings support that fiber consumption prevented the development of hypertension by rebalancing of dysfunctional gut-immune system-vascular wall axis in SLE.
Authors’ response: Bias in the vaccine effectiveness estimates of one-dose post-exposure prophylaxis against mpox
Authors: Laura Montero Morales, José Francisco Barbas del Buey, Marcos Alonso García, Jesús Iñigo Martínez, Noelia Cenamor Largo, Susana Jiménez Bueno, Araceli Arce Arnáez
Journal: Eurosurveillance (2023)

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A systematic analysis of the human immune response to Plasmodium vivax
Authors: Florian A. Bach, Diana Muñoz Sandoval, Michalina Mazurczyk, Yrene Themistocleous, Thomas A. Rawlinson, Adam C. Harding, Alison Kemp, Sarah E. Silk, Jordan R. Barrett, Nick J. Edwards, Alasdair Ivens, Julian C. Rayner, Angela M. Minassian, Giorgio Napolitani, Simon J. Draper, Philip J. Spence
Journal: Journal of Clinical Investigation (2023)

BACKGROUNDThe biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence.METHODSParticipants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies.RESULTSP. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous CD4+ T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease.CONCLUSIONP. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03797989.FUNDINGThe European Union's Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society.
Antimicrobial susceptibility testing and reporting practices of public hospital microbiology laboratories in Greece, 2022: A national observational survey and call for action
Authors: Sofia Karagiannidou, Ioannis Kopsidas, Michalis Polemis, Kyriaki Tryfinopoulou, Theoklis Zaoutis
Journal: Eurosurveillance (2023)

Antimicrobial resistance (AMR) in Greece is among the highest across the European Union/European Economic Area (EU/EEA), with high AMR rates even to last-line antibiotics. To better understand the clinical microbiology laboratory practices and capacities in species identification and antimicrobial susceptibility testing (AST) across public healthcare establishments in Greece, we sent a questionnaire to 98 of 128 public hospital microbiology laboratories between 1 February and 1 April 2022. Of the 73.5% (72/98) that responded, 51.4% (37/72) reported using EUCAST guidelines. Two of three laboratories used an automated instrument for species identification and AST for all laboratory samples. Broth microdilution for colistin susceptibility testing was used by 46 of the laboratories, more frequently in larger (> 400 beds) versus smaller (< 400 beds) hospitals (90.5% (19/21) vs 52.9% (27/51) respectively, p = 0.011). MALDI-TOF mass spectrometry was available in one of 10 laboratories, and more often in larger compared to smaller hospitals (p = 0.035). Although the majority of laboratories had a laboratory information system (LIS) in place, only half had the capacity to extract data directly from the LIS for the purpose of AMR surveillance; 73.6% (53/72) used restrictive antibiograms. Public microbiology laboratory AMR capacities in Greece require improvement, prioritising interventions for EUCAST guidelines implementation.
Real-world data show improved melanoma survival in Sweden
Authors: Magdalena Claeson
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Real-world data show improved melanoma survival in Sweden Get access Magdalena Claeson Magdalena Claeson Conceptualization, Funding acquisition, Writing - original draft, Writing - review & editing Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia Email: magdalena.claeson@vgregion.se https://orcid.org/0000-0001-5021-323X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad309, https://doi.org/10.1093/bjd/ljad309 Published: 24 August 2023 Article history Received: 18 August 2023 Accepted: 19 August 2023 Published: 24 August 2023 Corrected and typeset: 15 September 2023